SAMe is a water-soluble physiologically active substance occurring widely in living organisms and playing a key role as a methyl donor involved in the methylation by a wide range of transmethylase in the synthesis and metabolism of nucleic acid, neurotransmitter, phospholipid, hormone, protein, or the like. SAMe is observed in almost all human cells, serves as a cofactor in various biochemical reactions, and is metabolized through three metabolic pathways: transmethylation, transsulfuration, and transaminopropylation. For example, SAMe is an essential substance for the maintenance of cartilage and the biosynthesis of brain chemicals. A recent function study has reported that SAMe has a therapeutic effect on fatty liver, hyperlipemia, arteriosclerosis, insomnia, alcoholic hepatitis, senile dementia, and the like. As just described, SAMe is an important physiologically active substance and is widely used in Euramerican countries as a therapeutic agent for depression, liver disorder, arthritis, and the like or as a health food.
Therefore, it is strongly desired that SAMe be produced and supplied conveniently and inexpensively. Conventionally, the well-known methods of producing SAMe include a fermentation method of using a culture medium containing L-methionine precursor, an enzymatic synthesis method of allowing substrates: adenosine 5′-triphosphate (ATP) and L-methionine to interact with SAMe synthase (methionine adenosyltransferase) isolated and purified from microorganisms, such as yeast, and a chemical synthesis method.
The enzymatic synthesis method, in which SAMe is enzymatically synthesized by allowing substrates: adenosine 5′-triphosphate (ATP) and L-methionine to interact with SAMe synthase (methionine adenosyltransferase) isolated and purified from microorganisms, such as yeast, has the advantage that SAMe is accumulated in large quantities and not required to be extracted from yeast cells, as compared with the fermentation method. However, this method has various problems including the complex preparation of enzymes, the low activity of obtained enzymes, the necessity of removing interfering substances, such as ATPase, and the extremely high cost of ATP as a substrate, and therefore cannot necessarily be a practical method. In addition, the recent progress of genetic engineering has led these enzymes to be prepared more conveniently by using cloned SAMe synthase genes so as to solve the problems involved in the preparation of enzymes. However, high-cost ATP still needs to be used as a substrate, and other practical problems have not been solved.
Furthermore, SAMe is thermolabile and easily degradable even at normal temperature, this presenting a major obstacle to its application to a medicine and a health food. To eliminate this problem, numerous attempts have been made to improve the storage stability. For example, a method is commonly used in which SAMe composition obtained by the above-mentioned production method is purified through chromatography or the like, and then converted into a salt of sulfuric acid, p-toluenesulfonic acid, or butanedisulfonic acid to stabilize SAMe (see Patent Document 1), or in which the purified SAMe is added with an additive to give a stabilized SAMe composition (for example, see also Patent Document 1). These methods require great time and expense and therefore have great difficulty in producing and providing important SAMe inexpensively as a therapeutic agent and a health food. Recently, studies have been made on SAMe-containing dry microorganisms by using orally available microorganisms having an ability to produce SAMe more conveniently and more inexpensively with fewer steps of purification (for example, see Patent Document 2 and Non-Patent Document 2). At the present time, however, SAMe-containing dry microorganisms involves a problem of lower storage stability than purified SAMe and SAMe compositions.